INSULIN ISOLATION FROM HEROPHILUS TO LANGERHANS AND BANTING EARLY ANATOMY AND PHYSIOLOGY OF PANCREAS AND THE UNIVERSITY OF ADELAIDE CONTRIBUTION

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1 INSULIN ISOLATION FROM HEROPHILUS TO LANGERHANS AND BANTING EARLY ANATOMY AND PHYSIOLOGY OF PANCREAS AND THE UNIVERSITY OF ADELAIDE CONTRIBUTION

2 HISTORY: MAJOR CONTRIBUTORS: EGYPT, GREECE, ROME, BELGIUM, FRANCE, GERMANY, CANADA AND AUSTRALIA HEROPHILUS BCE GALEN ? 216 CE VESALIUS WIRSUNG, SANTORINI, VATER DE GRAAF CLAUDE BERNARD LANGERHANS BANTING THOBURN BRAILSFORD ROBERTSON

3 ALEXANDRIA AND HEROPHILUS BCE DYNASTY OF PTOLEMIES FOLLOWED ALEXANDER IN 323 AND CONTINUED TO SUPPORT SCIENCES AND CULTURE. ANATOMY THRIVED BECAUSE HUMAN DISSECTION WAS POSSIBLE. HEROPHILUS PERFORMED MANY DISSECTIONS, SOME IN PUBLIC AND WAS THE FIRST TO DESCRIBE THE PANCREAS HEROPHILUS LIBRARY IN ALEXANDRIA

4 GALEN (CE ) STUDIED MEDICINE AT THE AESCULAPIUM IN PERGAMON VISITED CENTRES OF LEARNING, THOUGHT PANCREAS PROTECTED BLOOD VESSELS SURGEON TO GLADIATORS 161 MOVED TO ROME MARCUS AURELIUS SUPPORT DISSECTIONS OF ANIMALS NUMEROUS PUBLICATIONS WHICH INFLUENCED ANATOMY FOR 1500 YEARS

5 CHRONOLOGY GRECO-ROMAN ERA: HEROPHILUS AND GALEN BCE TO 800 CE DARK AGES: ARABIC GOLDEN AGE, IBN SENA (AVICENNA) MEDICAL RENAISSASNCE: VESALIUS 1514 TO 1546 WIRSUNG AND SANTORINI VATER AND BRUNNER DE GRAAF AND BERNARD MICROSCOPE AND VITAL STAINS: LANGERHANS 1869 DISCOVERY OF INSULIN: BANTING, BEST, MCLEOD AND COLLIP NOBEL PRIZE 1923 ROBERTSON MASS PRODUCES INSULIN IN ADELAIDE, c. 1924

6 PANCREAS? ANDREAS VESALIUS THESE WOODCUT FIGURES APPARENTLY DEPICT THE PANCREAS WHICH IS NOT NORMAL OR DESCRIBED CLEARLY IN THE DE HUMANI CORPORIS FABRICA

7 DRAWINGS OF A PANCREAS BY EUSTACHIUS AND DE GRAAF. EUSTACHIUS PROBABLY DREW A DOG PANCREAS, DE GRAAF S DRAWING HAS ONLY ONE DUCT. SANTORINI DESCRIBED THE ACCESSORY DUCT LATER BARTOLOMEO EUSTACHIO REINIER DE GRAAF

8 ANATOMY AND EXOCRINE FUNCTION WIRSUNG AND SANTORINI DESCRIBED PANCREATIC DUCTS BRUNNER AND VATER DESCRIBED THE AMPULLA DE GRAAF COLLECTED PANCREATIC JUICE FROM DOG CLAUDE BERNARD NOTED THE EFFECT OF ENZYMES AWARDED A PRIZE FROM THE FRENCH ACADEMY OF SCIENCES

9 TITLE PAGE FROM DE GRAAF S TREATISE ON PANCREATIC JUICE AND ITS COLLECTION FROM A PANCRETIC FISTULA IN A DOG.

10 DE GRAAF DE GRAAF HAD SEVERAL ATTEMPTS TO PRODUCE A FUNCTIONING FISTULA. THOUGHT THE JUICE TO BE ALKALINE AND POSSIBLY THAT THE FLOW INCREASED DURING FEEDING. BIOCHEMISTRY WAS PRIMITIVE A DOG WITH A FISTULA COLLECTING APPARATUS

11 PAUL LANGERHANS THESIS AT THE BERLIN PATHOLOGICAL INSTITUTE 1869 HISTOLOGY OF A SINGLE PANCREATIC ISLET, CENTER

12 ANATOMY AND ENDOCRINE FUNCTION LANGERHANS DESCRIBED THE ISLETS BUT THOUGHT THEY MAY BE LYMPHATIC TISSUE LANGUESSE SUGGESTED THE NAMING OF THE ISLANDS AFTER LANGERHANS AND BELIEVED THE PLAYED AN IMPORTANT ROLE MINKOWSKI AND VON MEHRING REMOVED CANINE AND PRODUCED DIABETES BARROW PRODUCED PANCRERATIC FIBROSIS BY LIGATING THE PANCRETIC DUCT IN DOGS BANTING, BEST, MACLEOD AND COLLIP ISOLATED INSULIN

13 THE TORONTO INSULIN TEAM BANTING ORTHOPOEDIC SURGEON, ISOLATED INSULIN BEST MEDICAL STUDENT BANTIGS COLLABORATOR BANTING AND GEST WITH THEIR DIABETIC DOG MACLEOD PROFESSOR OF PHYSIOLOGY COLLIP BIOCHEMIST

14 ISOLATION OF AN INSULIN CONTAINIG PROTEIN BANTING GRADUATED IN MEDICINE AND VOLUNTEERED IN WW1 (1918). HE RECEIVED A MILITARY MEDAL FOR BRAVERY UNDER FIRE AT CAMBRAI. BEST WAS IN A TANK REGIMENT. ON RETURN BANTING BECAME A PAEDIATRC ORTHPOEDIC SURGEON, BUT ALSO LECTURED IN PHARMACOLOGY. BEST BECAME A MEDICAL STUDENT. BANTING CONTINUED HIS INTEREST IN PANCREAS. AT THIS TIME MANY TRIED TO ISOLATE INSULIN BUT FAILED. BANTING FELT THAT THE PROTEOLYTIC ACTION OF PANCREATIC ENZYMES INTERFERED WITH THE PROCESS. HE WAS AWARE OF MINKOWSKI AND BEHRING S WORK IN PRODUCING DIABETES IN DOGS AFTER TOTAL PANCREATECTOMY.

15 ISOLATION OF AN INSULIN CONTAINIG PROTEIN HE ALSO FELT THAT MOSES BARROW S PUBLICATION (1920) ON PANCRETIC FIBROSIS AFTER DUCT LIGATION WAS IMPORTANT IN REDUCING THE ENZYME EFFECT. HE BELIEVED THAT REMOVING DOGS PANCREASES TO PRODUCE DIABETES AND USING A FIBROSED PANCREAS TO EXTRACT THE TISSUE WITHOUT THE ENZYMES COULD WORK. HE APPROACHED PROFESSOR MACLEOD AND AFTER SOME DEBATES HE WAS ALLOWED 10 DOGS AND AND BEST AS ASSISTANT. THE TISSUE FROM THE FIBROTIC PANCREASES WAS SLICED, MINCED AND DISSOLVED. IT WAS ALSO COOLED UNDER ICE SLUDGE AND THEN INJECTED INTO DIABETIC DOGS. THE RESULTS RESULTED IN A NOBEL PRIZE AWARD

16 PATHOLOGY (1962) 14, pp DOG PANCREAS DRAWING BEFORE LIGATION OF THE CRANIAL HALF, LEFT. PHOTOGRAPH OF FIBROSED CRANIAL HALF, RIGHT. IN THIS DOG ONLY THE CRANIAL DUCT WAS LIGATED. BANTING LIGATED BOTH DUCTS AND THUS MARKEDLY REDUCED THE ENZYME PRODUCTION.

17 PAGE 966 FROM BEST AND TAYLOR PHYSIOLOGY The chart shows glucose levels on the vertical axis and the dates and years above. The glucose levels are from a diabetic dog after a total pancreatectomy. The first arrow (August ) indicates the injection of Bantings pancreatic extract and the glucose level fell to below 10. Twelve hours later as the glucose level rises, extract which was INCUBATED with pancreatic juice was injected with no effect, but re-injection with the pure extract lowered the glucose level again.

18 LIKELY REASONS FOR INCREASE IN KNOWLEDGE IN ANATOMY AND FUNCTION OF PANCREAS RELAXATION OF REGULATIONS PROHIBITING DISSECTION ESTABLISHMENT OF SCHOOLS OF LEARNING TRANSLATIONS OF ORIGINAL GREEK AND OTHER TEXTS DEVELOPMENT OF THE PRINTING PRESS RENAISSANCE IN ANATOMY AND EXPLORATION ADVANCES IN ALLIED SCIENCES: MICROSCOPY, BIOCHEMISTRY AND OTHER TECHNOLOGIES)

19 CONCLUSION 2000 YEARS FROM PANCREAS DISCOVERY TO INSULIN ALEXANDER THE GREAT, THE PTOLEMIES AND GALEN RENAISSANCE : PRINTING, LATIN, NEW TECHNOLOGIES ATTEMPTS TO DRAW PANCREAS: VESALIUS, EUSTACHIUS EXOCRINE FUNCTION: DE-GRAAF AND CLAUDE BERNARD ENDOCRINE ROLE: LANGERHANS AND LAGUESSE, MNKOWSKI, MEHRING, BARROW THE INSULIN TEAM

20 THE VITAL ROLE OF DOGS PARKER AND SCRUFFY NETWORKING (LT), PARKER AND PASSING BIGGER DOG AND CARER (RT) MANY DOGS WERE KILLED/SACRIFICED TO ISOLATE INSULIN THEY SHOULD BE REMEMBERED.